New Bis-Cresol-Bridged <i>bis</i>(1,4,7-Triazacyclononane) Ligand As Receptor for Metal Cations and Phosphate Anions

The synthesis and characterization of a new bis([9]aneN3) ligand (H2L) containing two [9]aneN3 macrocyclic moieties separated by a 2,2′-methylene-bis-cresol (cresol = 4-methyl-phenol) unit is reported. A potentiometric and 1H NMR study in aqueous solution reveals that H2L is in a zwitterionic form, and protonation of the cresolate oxygens occurs only with the formation of the highly charged (H5L)3+ and (H6L)4+ species at acidic pH values. The coordination properties of H2L toward Cu(II), Zn(II), Cd(II), and Pb(II) were studied by means of potentiometric and UV spectrophotometric measurements. The ligand gives both mono- and binuclear complexes in aqueous solution. At acidic pH values the ligand forms stable binuclear [M2H2L]4+ complexes, where each metal is coordinated by two amine groups of [9]aneN3 and the deprotonated oxygen of the adjacent cresol unit; the remaining amine group is protonated. Deprotonation of the [M2H2L]4+ species at alkaline pH values affords [M2L]2+ complexes, where all amine groups of the [9]aneN3 moieties are involved in metal coordination. Binding of mono-, di- and triphosphate, and adenosine triphosphate (ATP) was studied by means of potentiometric, 1H and 31P NMR measurements and by molecular dynamics simulations. The receptor forms stable 1:1 adducts with di-, triphosphate, and ATP, while the interaction with monophosphate is too low to be detected. In the complexes both the [9]aneN3 moieties act cooperatively in the substrate binding process. The stability of the adducts increases in the order diphosphate < triphosphate < ATP. This trend is explained in terms of increasing number of charge−charge interactions between the phosphate chains and the protonated [9]aneN3 subunits and, in the case of ATP, of stacking interactions between the adenine and cresol units.本文报道了一种新型双(1,4,7-三氮杂环壬烷([9]aneN3))配体(H2L)的合成与表征，该配体包含两个被2,2'-亚甲基双甲酚（甲酚=4-甲基苯酚）单元隔开的1,4,7-三氮杂环壬烷([9]aneN3)大环单元。通过水溶液中的电位滴定与1H核磁共振（1H NMR）研究发现，H2L以两性离子形式存在；仅当在酸性pH条件下生成带高电荷的(H5L)3+与(H6L)4+物种时，甲酚氧基才会发生质子化。本文通过电位滴定与紫外分光光度法，研究了H2L对Cu(II)、Zn(II)、Cd(II)及Pb(II)的配位性能。该配体在水溶液中可形成单核与双核两种配合物。在酸性pH条件下，配体会生成稳定的双核[M2H2L]4+配合物：每个金属离子均与1,4,7-三氮杂环壬烷([9]aneN3)的两个胺基以及相邻甲酚单元的去质子化氧原子配位，剩余的胺基则发生质子化。在碱性pH条件下，[M2H2L]4+物种发生去质子化，转化为[M2L]2+配合物，此时1,4,7-三氮杂环壬烷([9]aneN3)单元的所有胺基均参与金属配位。本文通过电位滴定、1H与31P核磁共振（31P NMR）测量以及分子动力学模拟，研究了单磷酸、二磷酸、三磷酸与三磷酸腺苷(ATP)的结合行为。该受体可与二磷酸、三磷酸及ATP形成稳定的1:1加合物，但其与单磷酸的相互作用过弱，无法被检测到。在该类配合物中，两个1,4,7-三氮杂环壬烷([9]aneN3)单元在底物结合过程中协同发挥作用。加合物的稳定性按二磷酸 < 三磷酸 < ATP的顺序递增。这一趋势可归因于：磷酸链与质子化1,4,7-三氮杂环壬烷([9]aneN3)亚基之间的电荷-电荷相互作用数量逐渐增加；而对于三磷酸腺苷(ATP)来说，还存在腺嘌呤与甲酚单元之间的堆叠相互作用。